The immune, endocrine and nervous systems are integrated due to the existence of reciprocal pathways for transmitting information about changes in their actual functional state. The main task of the brain is to receive, integrate and store information, and there is strong evidence that this also applies to information obtained through the body’s immune responses. It has been proven that the production of cytokines in the brain can be caused not only by peripheral immune stimulation, but also by the nerve cells themselves, stimulated by certain neurosensory signals. Evolutionarily preserved antihomeostatic mechanisms characteristic of specific diseases are the subject of further research, the results of which may be very important for the development of therapeutic strategies that would prevent the undesirable combined effects of immune and neuroendocrine mediators.

BACKGROUND: The level of iodine consumption by the population largery determines the spectrum of thyroid pathology. To date, in the Russian Federation, iodine-deficiency disorders (IDD) occupy a leading position in the structure of all thyroid diseases. Chronic ID leads to adverse health consequences and significant economic costs for their elimination on a national scale. However, the spectrum of thyroid pathology is not limited to the problem of ID, and the study of other thyroid diseases is also of interest.
AIMS: to assess the dynamics of prevalence and incidence of IDD and other thyroid diseases in the entire population of the RF for the period 2009–2018, using official state statistics.
MATERIALS AND METHODS: the main epidemiological indicators (incidence and prevalence) of thyroid diseases in the entire population of the RF were analyzed using official state statistics. The analyzed period is 2009–2018. There was no medical intervention. To assess the dynamics of prevalence and incidence, a linear regression models were constructed, the slope of the trend line was calculated.
RESULTS: the data were analyzed in accordance with the structure of diseases presented in the statistical reporting: goiter, thyroiditis, hypothyroidism, thyrotoxicosis, congenital iodine deficiency syndrome. For the ten-year period 2009–2018 there is a statistically significant increase in the prevalence of various forms of goiter, thyrotoxicosis, congenital iodine deficiency syndrome in the entire population of the Russian Federation. During the observation period, an increase in the incidence of thyrotoxicosis was revealed. With regard to the incidence of congenital iodine deficiency syndrome, only an upward trend was revealed. Despite the fact that during the observation period the number of new cases of various forms of goiter decreased, the prevalence of goiter among the population of the Russian Federation remains high: 1.2% of the population by January 1, 2019. with the growth of autoimmune pathology, improvement of the level of diagnosis, and also, in some cases, with overdiagnosis (for example, when diagnosing autoimmune thyroiditis in individuals with asymptomatic carriage of antithyroid antibodies). The current approaches to iodine prophylaxis are not effective enough.
CONCLUSIONS: the results of the analysis indicate mainly an increase in the high prevalence of thyroid pathology among the population of the RF against the background of regional events. The problem of ID remains unresolved, which dictates the need to introduce universal mandatory salt iodization in the territory of the RF.

The exponential rise in the use of immune checkpoint inhibitors (Ipilimumab, Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab, and Avelumab) as the new standard for cancer treatment increase the incidence the immune-related adverse events due to immune activation. Endocrine immune-related adverse events are the third most commonly reported. Thyroid gland is most susceptible to autoimmune dysfunctions from immune checkpoint inhibitors and associated with the use of anti-PD-1 monoclonal antibodies. Hypophysitis develops more often during therapy with anti-CTLA-4 monoclonal antibodies. But such immune-related adverse events as diabetes mellitus, hypoparathyroidism are rare (about 1% of cases).
We present a clinical case of the patient with skin melanoma who was prescribed therapy with immune checkpoints inhibitors (Pembrolizumab). Immune-related adverse events developed with damage to the endocrine organs after 3 Pembrolizumab injections. Of greatest interest is the development of two endocrine immune-related adverse events at once: destructive thyroiditis (with a short phase of thyrotoxicosis and subsequent persistent hypothyroidism) and diabetes mellitus. We tried to reflect the chronology of diseases and their features as fully as possible for endocrinologists, oncologists, therapists, family doctors and other medical doctors of related specialties.

The cystic fibrosis transmembrane regulator (CFTR) gene encodes the synthesis of a protein of the same name, which functions as a direct activator of anionic transport. Chloride is the most abundant anion; as an antagonist of Na⁺ and K⁺, it provides electroneutrality of cell membranes at rest; together with cations, it serves as an important osmolyte and forms water flow across cell membranes for transepithelial secretion.
Glandular cells in CF trap Cl^– and Na⁺, and the prodused secretion is excessively viscous. Subnormal CFTR activity leads to stagnation of mucociliary clearance, inhibition of intestinal transport.
In addition to exocrine disorders, CFTR mutations are associated with a decrease in volume, mass, increased apoptosis of β-cells of the pancreas, a significant suppression of insulin exocytosis in response to stimulation with glucose and glucagon-like peptide-1, hyperglucagonemia against the background of a defect in the suppression of α-cell function by insulin, but a decrease in maximum capacity α-cells.
Deficiency and progressive decline in bone mineral density is an expected secondary manifestation of CF due to pancreatic exocrine insufficiency with malabsorption of nutrients and fat-soluble vitamins. However, in patients with the F508del mutation, a significant decrease in the synthesis of OPG, COX-2, PGE2 in the osteoblastic formation, and an increase in the activity of the antianabolic NF-kB were found. We are talking about a defect in the canonical signaling pathway (Wnt/β-catenin), which regulates the expression of genes-activators of osteoblastogenesis, dissociation of the stages of physiological bone remodeling.
In addition to congenital bilateral or unilateral aplasia of the vas deferens, an increase in the frequency of CFTR mutations is also found in non-obstructive azoospermia, oligo-, astheno- and teratospermia. CFTR is involved in the entry of HCO₃^– into Sertoli cells to trigger cAMP-dependent transcription and its defects lead to suppression of FSH-dependent gene expression of spermatogenesis, loss of sequence in the Wnt cascade, destruction of the PGE2-dependent transepithelial interaction and, as a consequence, the blood-testicular barrier.
CF is characterized, along with classical signs, by endocrine dysfunction of the pancreas, osteoporosis with suppression of osteoblastogenesis, and a defect in spermatogenesis.

BACKGROUND. Primary hyperparathyroidism (PGPT) is an increase in the secretory activity of the parathyroid glands (OSH), due to their tumor or hyperplastic changes. Due to the lack of an effective alternative to the treatment of PGPT, the surgical method is still the only correct tactical solution for the management of patients with an established diagnosis of PGPT. The paper presents the long-term results and assessment of the quality of life of patients who underwent surgical treatment from standard and small access. The results obtained showed the promise of a sparing approach to the treatment of PGPT caused by LV adenoma.
AIM. To study the effectiveness of surgical treatment of patients with PGPT based on the assessment of the quality of life of patients who underwent parathyroidectomy from standard and small access.
MATERIALS AND METHODS. A retrospective study of the quality of life of patients with PGPT after surgical treatment was conducted using the SF-36 questionnaire and the linear analog scale (LAS). Statistical data processing is performed in the R programming language using the FMSB package. The quantitative parameters were presented as median (Median) and interquartile range (25th (1^st Qu) — lower quartile and 75th (3^rd Qu ) — upper quartile). As a nonparametric statistical criterion, the Mann–Whitney U-test was used, on the basis of which the p-value was calculated. The calculated data of the research results are presented in graphical form — in the form of bar charts, spider plot and barplot.
RESULTS. This study involved 264 patients. The patients were divided into 2 groups: GR1 — patients operated from the Kocher access with mandatory revision of all 4 OSH, GR2 — patients who received surgical treatment from the small access with the removal of the altered OSH, without revision of the remaining OSH. When analyzing the quality of life of patients before surgery, there were no statistically significant differences in the groups in terms of PF (Physical Functioning) and VT (Vitality). Small-access parathyroidectomy (patients with GR 2) significantly improved the quality of life in the GH (General Health) and VT (Vitality) domains. The analysis of LAS before surgery between the groups showed no statistically significant differences, while after surgical treatment, the indicators on the linear analog scale differ in the direction of improvement in GR2.
CONCLUSION. The results obtained in the course of the study showed the promise of a gentle approach to the treatment of PGPT caused by LV adenoma, which is reflected in higher quality of life indicators.

In this case report the authors inform about late diagnosis of giant adenoma of the parathyroid gland with primary hyperparathyroidism (PHPT) and the development of fibrocystic osteitis with a «brown» tumor of the upper jaw. The patient has been under the care endocrinologist with type 2 diabetes mellitus and multinodular goiter for 8 years.
The last 5 years there was a clinical manifestation of PHPT, but the diagnosis was made by an oncologist after the detection of a «brown» tumor of the upper jaw. According to multispiral computed tomography and scintigraphy with 99mTc-MIBI, a focal lesion was found in the upper jaw on the right, lytic foci in the bones of the cranial vault, pelvis, lower extremities, ribs on the right, as well as a giant parathyroid adenoma on the right. According to the increased risk of the patient having a malignant neoplasm of the parathyroid gland, an extended surgical treatment of PHPT in the enblock volume was carried out with the achievement of remission of the PHPT. This clinical case illustrates a variant of the severe course of PHPT with the development of such a rare complication as fibrocystic osteitis and demonstrates the importance of timely diagnosis.

Acute and chronic thyroid diseases are the most frequently detected disorders being second only to diabetes mellitus.
The World Health Organization points out that thyroid diseases’ incidence tends to grow every year. The present paper consists of clinical practice guidelines that consider etiology, clinical course, diagnostics and treatment of acute and chronic inflammatory thyroid diseases (except those of autoimmune type).
The clinical practice guidelines provide an important working tool for clinicians including specialty physicians and medical experts. Containing structured and concise information on the specific nosology, diagnostic methods and treatment tips these guidelines allow medical specialists to quickly resolve difficulties and choose the most efficient and personalized treatment (following strict principles of evidence-based medicine at the same time).
The clinical practice guidelines were drawn up by highly-skilled professional team of specialty physicians approved by the Expert Council of Russian Federation’s Health Department. These guidelines contain the most complete and up-to-date information required to diagnose acute and chronic thyroiditis, provide patient care and treatment.
The working group publishes the present paper in the professional journal dealing with endocrinology topics to improve healthcare quality and refine treatment of acute and chronic thyroiditis (autoimmune thyroiditis excluded). It is advisable to acquaint as many endocrinology and general (family) medicine specialists as possible with the full text of these clinical guidelines.

BACKGROUND. In Russian Federation, there are no large-scale cross-sectional multicenter epidemiological studies assessing the prevalence of vitamin D deficiency and insufficiency in different geographical latitudes. Insufficient solar insolation and inadequate vitamin D content in food dictate the need to study the epidemiological structure of low vitamin D status in Russia.
AIM. To assess the incidence of vitamin D deficiency and insufficiency among the population living in the regions of the Russian Federation located at latitudes from 45 ° to 70 °.
MATERIALS AND METHODS. The first stage of the Russian multicenter non-interventional registry study using the «crosssectional» method was carried out from March 2020 to May 2020.
RESULTS. In regions that represent a geographically representative sample of regions of the Russian Federation with a high risk of developing low levels of vitamin D, it’s deficiency was noted in 55.96%, and the level of deficiency and insufficiency was recorded in 84.01%.
CONCLUSION. Close attention to the wide scale of the problem of vitamin D deficiency and insufficiency in the Russian Federation will contribute to the progressive formation of various educational and preventive programs necessary to strengthen health and improve the quality of life of the population.

The frequent combination of type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) is an important socially significant and far from being studied problem. However, only a few works are devoted to it. To solve this problem, we analyzed the possible pathogenetic mechanisms from the standpoint of the impact on glucose homeostasis of the main hormones — insular and contrainsular.
The analysis was carried out using various literature databases, including Index Medicus, Scopus, Pub Med, Embase, Cochrane and others for the period, with rare exceptions, for 2000–2020, of which the works devoted directly to the aspect considered in this work were published in the last 5 years.
The analysis revealed a mutual aggravating effect of COPD and T2DM, in which COPD plays an initiating role. It also revealed a significant role of counterinsular hormones, which largely determines the nature of the pathogenesis of T2DM in COPD.
In addition, the article draws attention to the possible role of genetic factors that can be common for COPD and T2DM and have a significant role in the comorbidity of COPD and T2DM. The data obtained can be used for both diagnostic and therapeutic purposes in the correction of disorders of carbohydrate metabolism in COPD, which is the lot of further research.

BACKGROUND: Toxic nodular goiter (TNG) is a rare disease in which the cause of hyperthyroidism is the presence of a node or nodes that autonomously secrete thyroid hormones. With children and adolescents this condition is extremely rare — in 5–7.5% of all cases of nodular goiter. Therapy of toxic nodular goiter is aimed at relieving the symptoms of hyperthyroidism taking into account the malignant potential of the nodular formation. In the available literature, there are no data on the clinical course, comparative results of cytological and histological data in patients with toxic nodular goiter, which debuted in their childhood.
AIM: Analysis of the features of the clinical course, comparison of the results of cytological and histological studies of toxic nodular goiter in children and adolescents.
MATERIALS AND METHODS: A retrospective, single-center study of 21 patients with single-nodular toxic goiter, hospitalized at the Endocrinology Research Centre in the period from January 2016 to December 2019.
RESULTS: The mean age at the time of the survey was 13.9 years. Thirteen patients (65%) had manifest thyrotoxicosis, and seven (35%) had subclinical hyperthyroidism. More than half of children — 57.1% (n = 12) did not receive thyreostatic therapy. The cytological picture in 11 patients (61.1%) corresponded to benign changes (nodular colloid goiter or adenomatous goiter) — Bethesda II, in 4 patients — follicular tumor — Bethesda IV, in 4 children the study was not informative. 19 patients (90.5%) underwent surgical treatment (hemithyroidectomy). According to the results of histological examination, follicular adenoma was found in 44.4% of children with nodular toxic goiter with benign results of TAB (Bethesda II) and was found in 50% with revealing follicular neoplasia (Bethesda IV).
CONCLUSION: For the first time in the Russian Federation was carried out a comparative analysis of the characteristics of cytological and histological studies in children with toxic nodular goiter. It is significant that only in 10.5% (n=2) cytological and morphological results were consistent. The choice of radical treatment tactics should take into account the high frequency of mismatches between histological and morphological studies.

BACKGROUND: Today the problem of hyperandrogenism in women is a widely studied and discussed while same issue in relation to men is barely raised. In clinical practice, hyperandrogenism can be the cause of a number of diseases.
AIM: Provide characterization the variations of physiological hyperandrogenism in men.
MATERIALS AND METHODS: Сontinuous cross-sectional study of 100 men with hyperandrogenism. The study assessed the volume and structure of the prostate, the volume of the testicles; the levels of luteinizing hormone (LH), total testosterone, sex hormone binding globulin (SHBG) were determined with further calculation of the level of free testosterone according to Vermeullen, and dihydrotestosterone (DHT). Based on the results of the analysis of the hormonal status of patients with hyperandrogenism, 4 groups of patients were formed: 1-patients with increased total testosterone and SHBG levels; 2-patients with elevated total testosterone levels and normal SHBG levels; 3-patients with an increased level of total testosterone, DHT with a normal level of SHBG; 4-patients with an increased level of DHT with normal levels of total testosterone and SHBG. The difference between groups of patients was determined, a p-value <0.05 was considered statistically significant.
RESULTS: The age and volume of the prostate in group 1 patients were statistically significantly higher than in the other groups. This group, despite the high level of total testosterone, was not characterized by complaints of acne. Group 2 patients complained of acne more often, but the prevalence of this symptom even in this group was statistically significantly lower than in group 3 patients. At the same time, the frequency of occurrence of alopecia was statistically significantly lower in group 2 than in patients of both groups 3 and 4. Patients of group 3 had the most striking clinical manifestations of hyperandrogenism. Group 4 was characterized by alopecia.
CONCLUSION: An increase of androgen levels can be detected at any age. At the same time, in men of the older age group, an increase in the level of total testosterone may be due to an increase in the secretion of SHBG and not be accompanied by an increase in the level of free testosterone. In young patients, the clinical manifestations of hyperandrogenism may differ: patients with elevated DHT levels are characterized by androgenic alopecia; acne is common in men with elevated total and free testosterone levels, and increased DHT exacerbates the problem.